Introduction
had a prevalence of 6-fold higher than the
Age-related macular degeneration (AMD) is
60-64 year age group. It is estimated that
a disease of the macular retina that is the
the number of people with AMD will
main cause of permanent vision loss in
increase 60% by 2020.
people over the age of 50 years. AMD was
AMD classification is based on the
first described by Hutchinson and Tay in
criteria described by The International
the medical literature in 1875, as disease
ARM Epidemiological Study Group. Cheng,
with bilateral disorder that affects the
2009 states that AMD is a disturbance in
central
This
the macular region of the retina most
disease was recorded in the International
frequently encountered clinically in patients
Classification of Diseases, 10th revision
aged over 50 years. Based on clinical
(ICD-10) with the code H35.5 disease issued
manifestations, AMD is divided into 2 types:
by the World Health Organization.
non-neovascular
choroidoretinal
in
adults.
See, 1998 reported that the prevalence
or
dry
AMD,
and
neovascular or wet AMD.
and causes of blindness in many countries
Regillo, 2008 states that a typical sign of
including Indonesia are generally caused by
dry AMD is the presence of drusen, and
cataracts.
retinal
Different
things
happen
in
pigment
epithelium
(RPE)
developed countries such as UK, Australia
abnormalities in the form of geographic
and the USA that impaired vision mostly
atrophy and areas of hyperpigmentation.
resulted by AMD. In Indonesia, until now
Diagnosis of wet AMD can be enforced of the
there is no definite data about the incidence
presence of neovascularization, which is
and morbidity of AMD.
characterized by tissue proliferation and
Risk of AMD increases with age. Wang,
growth of new blood vessels that arise from
2007 stated that the Framingham Eye
the choroid into the retina or macula. As a
Study, found 6.4% of patients with age 65-
result
74 years and 19.7% at age above 75 years
submacular
have symptoms of AMD. In addition, the
accompanied by the formation of fibrotic
Eye Disease Prevalence Group reported
tissue
that
photoreceptor cells, resulting in permanent
in
the
United
States
population
prevalence of drusen have a minimum size
of
this
abnormal
haemorrhage
sub-or-intraretina
vessels
that
that
can
is
be
damage
blindness.
of 125  m at 6:12%, and prevalence of
Nowak, 2006 states that the AMD
advanced AMD is 1:47%. In accordance with
decreased diffusion of oxygen or metabolites
the Framingham Eye Study, this group also
to the macula, and this has been put
found that in patients aged above 80 years
forward as the beginning of a new blood
1
vessel formation. The most important thing
diseases and play a role in some cases
in the formation of new blood vessels is
accompanied
vascular endothelial growth factor (VEGF),
observed in Makassar by Abdullah N, 2007
preventing VEGF binding to its receptor can
on the disease endometriosis, Punagi Q,
lead to suppression and regression of newly
2007 in nasopharyngeal carcinoma, and Esa
formed blood vessels.
T, 2008 on diabetic retinopathy disease.
at
present,
however,
the
correlation
of
VEGF
gene
with the incidence and type of AMD. Results
Tuo, 2008) oxidative stress, (Seddon,
obtained from this study, expected to
2007) high-fat diet, (Ishida, 2006) and
provide
genetic
diagnostic
2007;
been
polymorphisms and serum VEGF levels
smoking, (Wong, 2008; Hughes, 2000;
(Scholl,
as
been no study in Indonesia, which reported
its
development is often associated with
factors.
angiogenesis,
To our knowledge, until now there has
The cause of wet AMD is still
unclear
by
De
additional
and
information
prognostic
of
in
the
disease
progression of AMD.
Almeida, 2009) Genetic researches
have revealed a relationship proinflammatory
genes,
such
Method
as
This was an observational study followed
complement factors H and B against
byl statistical analysis to examine the
the risk of AMD, about 75%. Fang,
relationship between VEGF gene promoter
2009 investigated on one of the genetic
polymorphisms and serum VEGF levels
factors recently been studied, namely
with the incidence and type of AMD.
the vascular endothelial growth factor-
Included in the case group is dry or wet
A (VEGF-A). He found an increased
AMD patients, whereas the control group is
the people above 50 years of age who do not
level of VEGF-A in tissue excision
from
the
membrane
neovascularization
suffer from AMD.
Choroidal
(CNV)
Identification of VEGF gene promoter
and
polymorphisms -460 and +405 positions
pigment epithelial cells of the macula
using primer pairs as follows: Position -460
in the early stages of AMD.
(CT): sense = 5 `-CCT CTT CCG GGG TAG
Some
researchers
have
found
a
GAG CCA-3 'and antisense = 5`-TGG CCT
significant correlation between VEGF gene
CCC TCT TCC GAC CGC-3 `. Position +405
polymorphisms (promoter region -460 and
(GC): sense = 5 `-CGA ATT CGG CTT GAG
+405) with the pathogenesis of many
GGG GC-3 'and antisense = 5`-GGG CGG
2
TGT CTG TCT GTC TG -3', with PCR
Medicine, and the last is a DNA sequencing
conditions of the Pre-denaturation step 94 °
at the Laboratory of Molecular Biology
c (5 min), followed by 35 cycles of PCR with
"Eijkman",
denaturation 94 ° c (30 seconds), annealing
examination and analysis of serum VEGF
62 ° c (30 seconds) and extension 72 ° c (30
levels of genetic progress within 3 months,
seconds), and 5 min final extension at 72 ° c.
from September to November 2010.
To identify the -460 polymorphism, the PCR
products
were
incubated
with
Jakarta.
The
series
of
Figure 1 is a plain and photo fluorescence
enzyme
retina in patients with AMD. In figure 1A we
BsaH1 and FaqI to +405, then do the
can see the drusen in the macular region,
visualization on 2% gel electrophoresis.
which
after
examination
followed
by
fluorescence angiography (1B) shows a shadow
Results
of submacular hyperfluorescence. It shows that
Explorative-study has been conducted case-
neovascularization has not happened yet, so
control test statistic to find the relationship
the diagnosis can be established as dry AMD.
of VEGF gene promoter polymorphisms and
The different fundus photograph is shown by
serum VEGF levels with the incidence and
the patient in Figure 1C, which shows the
type of Age-related macular degeneration. A
presence of soft confluent drusen accompanied
study of 66 people consisting of 12 wet
by
AMD, 17 dry AMD, and 37 control group
supports the diagnosis of wet AMD.
was
performed
situation
with the aim of research.
66 people comprising of 30 males (45.45%) and
Selection of subjects was conducted since
36 females (54.55%) with 51-60 years of age
January 2010 in the retinal outpatient
group as many as 31 people (46.97%), 61-70
department
Sudirohusodo
years old number 28 people (42.42%), and 71-
Hospital and Celebes Specialist Eye Clinic
80 years of 7 people (10.61%). The number of
"Orbita". Blood samples were collected
samples also consisted of wet AMD 12 people
followed by examination of serum VEGF
(18:18%), dry AMD 17 people (25.76%) as a
levels
group of cases, and 37 people (50.06%) who did
are
Wahidin
conducted
in
places
This
Table 1 is the characteristic data sample of
of
several
submakula.
in
accordance
at
bleeding
the
Clinical
Laboratory "Prodia", genetic analysis of
not suffer from AMD as the control group.
Polymerase Chain Reaction (PCR) and
Restriction fragment length polymorphism
Restriction Fragment Length Polymorphism
(RFLP) was done to identify the relationship
(RFLP) was undertaken at the Center for
between VEGF gene promoter polymorphism
Research Unit of Hasanuddin University
with incidence and type of AMD. Cutting the
and Research Unit of the Faculty of
DNA chain at position -460 then performed
3
DNA amplification using polymerase chain
sample with wild-type TT (95% CI 1.1 - 21.3).
reaction technique (PCR). Results PCR and
Samples with CC and CT polymorphism have
cutting the DNA chain by RFLP using
2.3 times greater risk to suffer from dry AMD
restriction enzyme BSAH1 consecutive can be
sample than with wild-type TT (95% CI 0.7-
seen in Figure 2 and 3.
7.6). Samples with CC and CT polymorphism
In Table 2 can be seen that the PCR
have 2.1 times greater risk to suffer from wet
product length 200 bp by cutting RFLP method
AMD than the sample with wild-type TT (95%
is divided into 3 groups, namely that no cut is
CI 0.4-10.6).
a wild-type with genotype TT, CT genotype
was
interrupted
in
part
by
a
Enzyme-linked
immunosorbent
assay
mutant
(ELISA) was performed to investigate the
heterozygote, and the cut was perfect with a
relationship between serum VEGF levels with
mutant genotype CC homozygote.
the incidence and type of AMD. Venous blood
Later in the table 3 it can be seen the
frequency
of
VEGF
gene
taken from the subjects of research, then
polymorphisms,
examined serum VEGF levels using ELISA.
namely TT as many as 33 people (50%), CT 31
Table 6 shows serum VEGF levels of all study
people (46.97%), and CC as much as 2 people
subjects. It can be seen that the levels of VEGF
(3:03%). After a successful cutting of DNA
in wet AMD is 263.73 +164.46 pg / ml, in dry
using restriction enzymes BSAH1, then do
AMD for 582 +557.54 pg / ml, and in control
grouping types of AMD to determine the
amounted to 65.52 +24.28 pg / ml.
distribution of VEGF gene polymorphisms in
To facilitate statistical analysis, the serum
the group of dry AMD, wet AMD, and control
VEGF levels are grouped on serum VEGF
groups.
levels > 100 pg/ml and <100 pg/ml. These
In table 4 can be seen a significant
standards proposed since there is no standard
correlation with p = 0.004 between VEGF gene
value of normal levels of VEGF, so that a
polymorphism with the type of AMD that
standard normal serum levels of VEGF in this
shows that the variation of CC genes found
study were serum levels of VEGF in the
only in wet AMD and was not found in dry
control group (mean = 65.52 + 24.28pg/ml), as
AMD and control.
shown in Table 7.
In Table 5 can be seen that subjects with
In table 8 can be seen elevated level of
CC and CT genotypes had 3.1 times greater
VEGF > 100 pg/ml was found in the group of
risk to suffer from wet AMD than samples with
wet and dry AMD, whereas in the control
TT genotype (95% CI 1.1-8.6). Subjects with
group level of VEGF <100 pg/ml by 37 (100%).
CC and CT polymorphism have 4.9 times
Statistically, the relationship of VEGF levels in
greater risk to suffer from wet AMD than the
the study expressed significant with p <0.001.
4
In table 9 can be seen that in the AMD
100%, and was not found at levels <100 pg/ml.
group there were 27 people (93.10%) with
In table 11 can be seen that the samples
VEGF levels > 100 pg/ml and only 2 people
with CC and CT polymorphism have 3.2 times
(6.90%) with levels < 100pg/ml. While in the
greater risk to have a serum VEGF levels >
control group, there were 37 people (100%)
100 pg/ml than the sample with the gene
who had VEGF levels <100pg/ml. There was a
variation TT. 95% confidence interval of 1.1-
significant relationship with p < 0.001 between
8.9.
VEGF levels with the incidence of AMD.
Subsequently performed statistical tests to
Subsequently performed statistical tests to
find the co-relationship between the VEGF
find the relationship of serum VEGF levels
gene polymorphism and serum VEGF levels
with the type of AMD. In table 9 shown that in
with the type of AMD. In table 12 can be seen
wet AMD group there were 10 people (83.33%)
that VEGF gene TT genotype in the control
with VEGF levels > 100pg/ml and 2 (16.67%)
group who had higher levels of < 100 pg/ml at
with levels < 100pg/ml. While in the control
95.83% and was not found at levels > 100
group, there were 37 people (100%) who had
pg/ml. In contrast to the CC polymorphism
VEGF levels < 100pg/ml. There is a significant
with type of wet AMD found levels > 100 pg/ml
relationship (p <0.001) between the levels of
by 100% and was not found at levels <100
VEGF with wet AMD. At the same table also
pg/ml.
revealed that there was significant correlation
In the CT polymorphism with wet AMD
(p <0.001) between the levels of VEGF with
found levels > 100 pg/ml by 37.5% and at levels
dry AMD. However, when compared with
<100 pg/ml of 6.67%. In the CT polymorphism
serum VEGF levels in wet and dry AMD, it is
with dry AMD is not found at levels < 100
seen that there were 10 people wet AMD
pg/ml. In contrast to the control group was not
(83.33%) with VEGF levels > 100pg/ml and
found at levels > 100 pg/ml.
only 2 people (16.67%) with levels <100pg/ml.
The relationship between the TT genotype
While the dry AMD group there were 17 people
of VEGF gene and VEGF serum levels with the
(100%) with VEGF levels > 100pg/ml. There
controls
was no significant relationship with p = 0081
significant
between VEGF levels with the type of AMD.
relationship between genotype CT VEGF gene
It can be seen in Table 10 that the TT
revealed
with
p
highly
<0.001,
statistically
as
does
the
polymorphisms and serum VEGF levels with
group, VEGF levels > 100 pg/ml 27.27%, and
the incidence of dry AMD.
<100 pg/ml at 72.73%. In the CT group VEGF
No statistical test can be done in groups of
levels > 100 pg/ml 51.61%, and <100 pg/ml at
VEGF
48.39%. In group CC VEGF levels > 100 pg/ml
because of the number of samples found in
5
gene
polymorphisms
CC
genotype
very few and only found in wet AMD.
Based on the characteristics of the study
sample (table 1), shows that the ratio of
Discussion
women than men at 55:45. Evans, 2005 and
Age-related macular degeneration (AMD) is a
Wang 2007, separately stated that based on
major cause of permanent visual impairment
the pooling and analysis of literature data
and blindness in adults, and remains a threat
shows women have a slightly higher risk of
in the next decade. Research on the AMD
developing AMD. Whether this is caused by life
developed rapidly in the late 20th century, and
expectancy was longer in women, or by
provides important information for the next
hormonal influences, or because of other
researches.
factors is still unanswered and more require in
In some observational studies including
depth analysis. Age as the sample of patients
case-control study based on clinical and
who are above 50 years of research. This is
population-based surveys, have consistently
consistent with the classification established
shown that family history is a risk factor on
by the International ARM Epidemiological
the incidence of AMD. Individuals with a
Study Group. In this study there are age group
family history with AMD have the risk ratio
51-60 years amounted to 46.97%. Although not
was 3 times higher than in people who have no
statistically significant different from the 61-
family history. (Wang, 2007)
70 year age group (42.42%), but something
Scholl and colleagues in 2007 reported the
similar was reported by The Baltimore Eye
number of candidate genes that are often been
Survey on prevalence data drusen patients
studied as genetic factor associated with AMD.
with diameters > 125 m at the white race.
Among candidate genes that they observe,
They reported that patients with drusen in age
VEGF is one of the gene that gave positive
group 55-59 years is slightly higher than the
result
AMD.
60-64 year age group, which then increased
This research was conducted to answer the
rapidly until age over 80 years. (Wang, 2007)
questions about the relationship of VEGF gene
Patients with AMD as the case group consisted
promoter polymorphisms and serum VEGF
of 12 people wet AMD (18.18%), and dry AMD
levels with the incidence and type of AMD.
as many as 17 people (25.76%). The control
VEGF gene polymorphism analysis included
group are individuals who do not suffer from
genotype at position -460 T/C, whereas VEGF
AMD as much as 37 people (56.06%). Serum
levels of analysis include the examination of
VEGF levels with values > 100 pg/ml by 27
serum VEGF levels, and the relationship with
people (40.91%), and less than 100 pg / ml was
VEGF gene polymorphism and serum VEGF
39 people (59.09%). There is a polymorphism
levels with the incidence and type of AMD.
on the variant distribution of wild-type TT 33
on
the
incidence
of
6
people (50%), mutant CT-heterozygote 31
Punagi Q, 2008, reported 15.62% in cases of
people (46.97%), and mutant-homozygote CC 2
nasopharyngeal carcinoma, and Esa T, 2008,
people (3.03%).
which
This research identified the VEGF gene
promoter
polymorphism
at
position
identifies
the
frequency
of
this
polymorphism by 7% in patients with diabetic
retinopathy.
-460,
although could not be disclosed at the position
In table 4 can be seen VEGF -460 genotype
+450. Henceforth, only discuss the VEGF gene
distribution. It appears that the frequency of
-460 polymorphism.
genotypes in wet AMD is TT = 3 (9.09%), CT =
Figure 2 shows the results of DNA
7 (22.58%), and CC = 2 (100%); in Dry AMD is
amplification by polymerase chain reaction
TT = 7 (21.21%), CT = 10 (32.26 %), and CC 0
(PCR). Shown in the electrophoresis results of
(0%), while the control group TT = 23 (69.70%),
white band with a length of 200bp on each slot
CT = 14 (45.16%), and CC 0 (0%). With no
is filled by a DNA sample. Furthermore, the
finding of polymorphisms homozygote (CC) in
results of these PCR conducted by restriction
dry AMD and control groups, can explain that
fragment length polymorphism (RFLP) with
the VEGF gene promoter -460 polymorphism
restriction enzyme BSAH1. Figure 3 shows the
had a significant correlation with the incidence
results of RFLP, that there are 3 types of
and type of AMD (p = 0.004). Significant
characteristic bands. Bands that do not cut in
correlation
the slots 3 and 5 is normal genetic variation
polymorphism has also been advanced by
(TT) with a length of 200bp. Slot 1,2 and 4
several researchers. Vannay, 2005 about his
contain DNA partially cut with a length of 200,
relationship with the incidence of retinopathy
178 and 22 bp. This indicates that the slot
of prematurity, and Churchill, 2006, who
contains
examines
the
genetic
variation
of
between
the
VEGF
relationship
AMD.
VEGF
polymorphisms
CC/homozygote which appears in the slot 6 is
distinguishes between the results obtained
the totally cut the DNA with a length of 178
from research to that done by Churchill is only
and 22bp. PCR and RFLP results can be seen
found in this study the results of VEGF -460
in table 2.
polymorphism alone, while Churchill and his
What
colleagues provide the results on 14 single
Table 3 shows the frequency of genetic
with 2
wet
of
-460
CT/heterozygote. The last variation is the
variation CC/homozygote
with
gene
patients
nucleotide polymorphisms from 45 patients
(3.03%) of the entire study population. This
with AMD and 94 age-matched control group
frequency is smaller than that found by
(p = 0.0074).
several researchers in Makassar. Abdullah N,
This study found odds ratios (OR) VEGF
2008 found 17.9% in cases of endometriosis;
gene -460 polymorphism in the CT and CC
7
genotype 3.1 times larger than the TT
the control group 65.52 + 24.28 pg/ml. High
genotype, as shown in table 5. Wang in 2007,
levels of serum VEGF compared to the Dry
also found in individuals with a family history
AMD Wet AMD due to hypoxia in the retinal
with AMD had a risk three times higher than
pigment epithelium (RPE). Kwak, 2000, which
in
history.
conducted research on the levels of VEGF in
Furthermore, at the same table can be seen
transgenic mice reported that hypoxic RPE
VEGF
CC
increased the incidence of CNV. Tschirch, 2009
genotype had 4.9 times the risk of suffering
states that VEGF has a hypoxic up-regulation
from wet AMD compared with the control, 2.3
on the vascular network. Increased levels of
times suffer from dry AMD compared to
VEGF may be an alarm for the occurrence of
controls, and 2.1 times suffer from wet AMD
hemodynamic compensation, and if the levels
compared with dry AMD. Szaflik, 2009 which
of VEGF started to decline indicating that the
specifically examine the distribution of VEGF
tissue oxygenation has been achieved.
people
who
gene
have
no
family
polymorphism
CT
and
gene -460 polymorphism in patients with AMD
Abdullah N in 2008 that conducts research
found that there was a significant correlation
on VEGF levels in patients with endometriosis
(OR 3.04, 95% CI 1.65-5.60) in the mutant
in Makassar obtain results that serum VEGF
genotype (CC + CT) to suffer from wet AMD
levels in the group case amounted to 334.18
than the group with TT genotype. They
pg/ml
concluded that VEGF gene -460 polymorphism
amounted to 91.36 pg/ml. Ozturk et al, 2009
may be considered as a potential sign on the
which make investigation of the influence of
incidence of wet AMD. Papis, 2009 which
serum cytokines and VEGF levels of diabetic
investigated the incidence of AMD in the
retinopathy (DR) and macular thickness was
Polish population sample of 177 patients with
also obtained similar results with our research.
wet AMD, 88 samples with dry AMD, and 136
They obtained the results of VEGF levels in
samples as a control group, reported that there
the control group amounted to 98.20 pg/ml,
is a relationship between the incidence of dry
compared with diabetic patients without DR at
AMD with genotype C/T (OR 3.77), and a weak
125.37 pg/ml, group NPDR 153.07 pg/ml, and
correlation between the incidence of dry AMD
the PDR group amounted to 149.12 pg/ml.
with the TT genotype (OR 0.19).
Tsai, 2006 also reported serum VEGF levels in
Table 6 shows the comparison of serum
compared
with
the
control
group
patients with wet AMD amounted to 256.0
VEGF levels in patients of wet and dry AMD
pg/ml and the control of 82.8 + 168.2 pg/ml.
with the control group. Levels of VEGF in wet
Table 8 shows the distribution of VEGF
AMD as much as 263.73 + 164.46 pg/ml, dry
levels > 100 pg/ml and <100 pg/ml on the type
AMD as much as 582.46 + 557.54 pg/ml, and
of AMD. VEGF levels were divided as high and
8
low limits based on the value of 100 pg/ml,
seen in table 9.
because until now there is no standard value of
Results obtained in this study reinforce
normal serum VEGF levels. VEGF levels > 100
previous results reported by Lip and colleagues
pg/ml in 83.33% of wet AMD, dry AMD 100%,
who examined the role of VEGF levels in
and 0% controls. VEGF levels < 100 pg/ml in
disease
16.67% of wet AMD, dry AMD 0%, and 100%
suggested that higher serum VEGF levels in
control. These results indicate that the entire
78 patients with AMD compared with age-
control group had higher levels of VEGF < 100
matched controls (p = 0.0196). They also found
pg/ml. Although there are 16.67% patients wet
that
AMD who had levels of VEGF <100 pg/ml, but
between dry and wet AMD. Different results
there were statistically significant differences
presented by Tsai, 2006. Although they found
between the levels of VEGF in the wet and dry
elevated levels of VEGF in 77 patients with
AMD compared with the control group (p
AMD compared to 42 controls (p <0.001), but
<0.001). The same thing was found by
there are significant differences higher in the
Abdullah N, 2008, that the serum VEGF levels
group of wet AMD compared with dry AMD (p
were significantly higher in patients with
= 0.004).
endometriosis compared with control group. (p
there
was
no
of
AMD.
significant
Lip,
2001
difference
Table 10 shows the distribution of VEGF
= 0.000).
This
progression
levels > 100 pg/ml and < 100 pg/ml of VEGF
study
also
significant
gene -460 polymorphism. It appears that the
correlation between serum VEGF levels with
CC genotype have 100% of VEGF levels > 100
wet AMD and dry AMD when compared with
pg/ml, while the TT genotype there were 24
the control group (p <0.001). Subsequently
(72.73%) VEGF levels are less than100 pg/ml.
performed
(p = 0011).
statistical
found
tests
a
to
find
the
relationship between serum VEGF levels in
In table 11 we can see that the VEGF gene
patients with wet and dry AMD. The results
polymorphism genotypes CT and CC have a
indicate that there were 83.33% of patients
relationship with increasing levels of serum
with wet AMD with serum VEGF levels > 100
VEGF. (OR 3.2, 95% CI 1.1-8.9).
pg/ml, and 16.67% with levels <100 pg/ml. In
In Table 12 showed that serum VEGF
contrast result was found in patients with dry
levels are less than 100 pg/ml and TT
AMD, that there was 100% with serum > 100
genotypes were mostly in the control group is
pg/ml. Pearson chi-square test found no
95.83% (p <0.001). Serum VEGF levels > 100
significant relationship between serum VEGF
pg/ml and genotype CC was found in patients
levels with the incidence of wet AMD when
wet AMD as much as 100%. Statistical tests
compared with dry AMD. (p = 0081), as can be
could not be done in the CC group because of
9
less number of samples, nevertheless can be
Although there are some limitations of the
seen that the CC group were only found in wet
study as described above but to our knowledge
AMD patients with VEGF levels > 100 pg/ml.
and based on literature study, to date there is
Results obtained in this study received the
no scientific work in Indonesia, which reported
tested hypothesis that VEGF gene promoter
on
polymorphism and serum VEGF levels have a
polymorphisms and serum VEGF levels with
relationship with AMD, VEGF gene promoter
the incidence and type of age-related macular
polymorphism
degeneration.
has
a
relationship
with
the
relationship
of
VEGF
gene
increasing levels of serum VEGF, which in
turn is co-related to the incidence and type of
Conclusions
age-related macular degeneration.
From the results obtained in this study, it can
However there are some limitations of the
be concluded that : the VEGF gene -460
study, such as : the study design is a case-
polymorphism of the nucleotide thymine (T) is
control
replaced by the nucleotide Cytosine (C), and
observational
study.
To
better
understand the relationship of VEGF gene
VEGF
polymorphisms and serum VEGF levels with
genotypes had a significant relationship to the
the incidence and type of AMD is required
incidence and type AMD (p = 0.004, OR = 3.1,
longitudinal cohort study. In this study only
95% CI 1.1-8.6). Levels of serum VEGF was
found type VEGF gene polymorphism at
higher in dry and wet AMD groups compared
position -460, so further molecular genetic
with the control group (p <0.001). There was a
testing is needed to examine the wider spread
significant correlation between serum VEGF
of VEGF gene haplotypes in more than 14
levels of patients with wet AMD with controls,
positions. In this study only examined the
as well as in patients with dry AMD (p <0.001).
relationship of VEGF gene polymorphisms
However, there is no significant correlation
with the incidence and type of AMD, which is
between serum VEGF levels of patients with
one of the genes involved in AMD. Other genes
wet AMD compared with dry AMD (p = 0081).
that have a strong relationship with AMD is
There was a significant correlation between
the CFH gene, LOC, CFB/C2, apoE, and
VEGF gene polymorphisms with serum VEGF
CX3CR1. The number of samples collected is
levels (p = 0011). There is a risk of elevated
very limited, consisting of 12 patients with wet
levels of serum VEGF in group CC and CT
AMD, 17 dry AMD, and 37 control group, so
genotypes (OR 3.2, 95% CI 1.1-8.9). There is a
there are limitations in statistical tests. To find
correlation
a significant relationship, it takes a larger
polymorphism
number of samples.
increase with the incidence and type of AMD.
10
gene
polymorphism
between
and
VEGF
serum
CT
and
gene
VEGF
CC
-460
levels
In order for the results of this study can be
useful both for future research and for the
benefit of medical services, need for further
studies to confirm the role and influence of
VEGF gene, VEGF gene -460 especially in the
pathogenesis of AMD, which could explain the
tendency of a person to suffer from AMD. More
in depth study with a larger number of
samples required to explain the mechanism of
VEGF-460 gene polymorphisms in relation to
the production of VEGF proteins. By obtaining
a significant correlation between VEGF gene
polymorphism with the incidence and type of
AMD (p = 0.004, OR = 3.1, 95% CI 1.1-8.6),
then the family of AMD patients should also be
analysis of VEGF gene for early detection and
preventive purposes against factor external
risks to prevent or inhibit disease progression
of
AMD.
Given
the
high
activity
of
angiogenesis characterized by increased serum
levels of VEGF in the group of AMD, the AMD
treatment needs to be studied more deeply,
especially the use of drugs Antiangiogenesis.
2006. VEGF polymorphisms are associated
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2008. Age-related macular degeneration.
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DC, et al. 2009. The role of molecular
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Ding X, Patel M, and Chan CC. 2009.
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Ehrlich R, Harris A, Kheradiya NS, et al.
2008. Age-related macular degeneration
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Esa T. 2008. Peranan gen vascular
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patogenesis retinopati diabetika. Laporan
Penelitian Risbin Iptekdok, Depkes
Ethen CM, Xiao F, Olsen TW, et al. 2005.
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